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Updated: May 21, 2026

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Hepatitis C virus-associated primary hepatocellular carcinoma in non-cirrhotic patients
Mazen Albeldawi1, Mohamed Soliman, Rocio Lopez
1Department of Gastroenterology and Hepatology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, USA.
Background:
There is limited literature on hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection in the absence of cirrhosis.
Aims:
To investigate the relationship between HCV and HCC in the absence of cirrhosis and to characterize patients with HCV infection presenting with HCC in the absence of cirrhosis.
Methods:
We identified all adult patients with histological confirmation of HCC between 1994 and 2007 (404 patients). A case-control design (four controls for each case with non-cirrhotic HCC) was chosen to compare characteristics and survival of HCV in HCC patients without (cases) and with (controls) cirrhosis. Conditional logistic regression analysis was used to identify factors independently associated with HCV in non-cirrhotic HCC.
Results:
Eighty-seven patients with non-cirrhotic HCC were identified, six (7 %) had HCV infection in comparison with 107 of 317 (55.7 %) with cirrhotic HCC (P < 0.001). Compared with the HCV-associated HCC cirrhotic group, patients with HCV-associated HCC in the absence of cirrhosis were more likely to present with a single nodule (100 vs. 66.7 %), larger nodule size (>5 cm) (100 vs. 16.7 %), and macrovascular invasion (66.7 vs. 17.4 %) at time of diagnosis. Four of six patients with HCV-associated HCC in the absence of cirrhosis where alive at three years (all had resection), which was better survival than for HCC arising in cirrhotic livers of HCV-infected individuals (66.7 vs. 39.1 %).
Conclusion:
We found that HCV is responsible for a small minority of non-cirrhotic HCC cases representing an uncommon and poorly defined subgroup of HCC.
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